WASHINGTON (Reuters) - It may be possible to predict whose
lung cancer is likely to come back after surgery has apparently
cured it, U.S. researchers reported on Wednesday.

And the findings could lead to more effective treatments
for lung cancer, a theory they are testing, the researchers
reported in the New England Journal of Medicine.

They saw clear changes in four genes in patients whose
cancer came back within five years after surgery and said the
findings might be used as the basis for a test.

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Patients found to have a high risk might consider special
chemotherapy after surgery.

"These people are at increased risk of recurrence. We think
that there are numerous ways that you can take care of them,"
said Dr. Malcolm Brock of Johns Hopkins University in
Baltimore, who led the study.

"One is of course more chemotherapy. But we also believe
that by giving them targeted therapies, new types of therapies,
we can help these patients," Brock said in a telephone
interview.

Brock's team tested 157 patients with stage I non small
cell lung cancer who had had small tumors surgically removed.

Of the patients, 51 had the cancer come back within 40
months -- just over three years -- while 116 stayed tumor-free.

The researchers found changes called methylation of the
promoter region in four genes among the patients whose cancer
returned. Methylation is a process that switches genes on and
off.

"The four genes of interest in our study are p16, CDH13,
APC, and RASSF1A. They are involved in cell-cycle control
(p16), invasion and metastasis (CDH13, APC), and Ras signaling
(RASSF1A)," the researchers wrote.

The researchers' test has been licensed to Belgian biotech
company OncoMethylome.

'DNA FORENSICS'

"This is DNA forensics for cancer," Brock said.

"All of these tumors that we are talking about are early
stage tumors. They are very small," he added. Yet a third of
patients with such tumors have their cancer return.

After surgery, it appears all the cancer is gone.
Pathologists look at the nearby tissue and lymph nodes under a
microscope and declare the patient cancer-free.

"But in 40 months the patient comes back with metastatic
disease in all of their body. How is that possible?" Brock
asked. "It must be that the microscope, which is a 17th century
innovation ... is not picking up all of the disease."

But the DNA test does, Brock believes. And the findings
could lead to new treatments for lung cancer, one of the
deadliest cancers.

Some drugs can home in on these changes however -- notably
drugs used to treat myelodysplastic syndromes, sometimes known
as pre-leukemia. They are known as hypomethylating agents and
include 5-azacytidine, decitabine and lenalidomide.

Brock's team is also testing these agents in lung cancer
patients. "There are lots of them and there are lots of
choices," he said.

He believes the test has wider uses. "We really think that
if this can be validated that it would have broader
applications to other solid tumors," he said.

"It gives weight to an idea that your tumor DNA and my
tumor DNA might be slightly different. It might even show us
ways that we can do personalized therapy."

Lung cancer kills more than 1 million people each year
worldwide. Only 15 percent of patients survive five years or
more.